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Barbara Murphy, MD is the Murray M. Rosenberg Professor of Medicine, Chair of the Department of Medicine for the Mount Sinai Health System and Dean for Clinical Integration and Population Health. Her area of interest is transplant immunology, focusing on the use of high throughput genomic technologies as a means to understand the immune mechanisms that lead to graft injury and loss, with the aim of identifying gene expression profiles and or genetic variants that may be used to predict those at greatest risk.

Dr. Murphy earned her M.B. B.A.O. B.Ch. from The Royal College of Surgeons in Ireland and went on to do an internship at Beaumont Hospital in Dublin. She completed a residency rotation at Beaumont Hospital followed by a fellowship in Clinical Nephrology also at Beaumont Hospital. Dr. Murphy completed her postdoctoral training with a fellowship in Nephrology at Brigham and Women's Hospital, Harvard Medical School. As part of this she trained in transplant immunology at the Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital, Harvard Medical School. Among her many honors, Dr. Murphy was awarded the Young Investigator Award in Basic Science by the American Society of Transplantation in 2003. In 2005, Dr. Murphy was awarded the Irene and Dr. Arthur M. Fishberg Professor of Medicine at The Mount Sinai Hospital. Then, in 2011, she was named Nephrologist of the Year by the American Kidney Fund. She received the distinguished Jacobi Medallion in 2014. She also received an honorary degree from University College, Dublin, Ireland. In 2016, Dr. Murphy was honored by The Annual Irish America Healthcare & Life Science 50.

Dr. Murphy belongs to a number of professional societies including the American Society of Transplantation and the American Society of Nephrology. Among her numerous achievements, she has held many leadership roles at a national level, including being a member of the Board of the American Society of Transplantation, the Executive Committee of the American Transplant Congress, and Chair of Education Committee of the American Society of Transplantation. Most recently, she served as the president of the American Society of Transplantation. In 2016, The American Society of Nephrology elected Dr. Murphy as its newest Councilor. In these positions, Dr. Murphy aims to directly impact patient care and access to healthcare, specifically, advocating for long-term coverage for immunosuppression.

Dr. Murphy is the Principle Investigator of a study, the Genomics of Chronic Renal Allograft Rejection, (GoCar), which aims to investigate the mechanisms leading to the development of transplant glomerulopathy, chronic arteriopathy funded through the NIH/NIAID Genomics Consortium in Transplantation. The GoCar study, recently published in The Lancet, examines gene expression profiles associated with the development of chronic rejection using microarray on protocol biopsies performed over two years following transplantation. In addition, a larger cohort of donor and recipient pairs are being enrolled to identify polymorphic variants of specific immunological genes which confer susceptibility to chronic rejection and the development of donor specific antibodies.

Dr. Murphy's Lab also investigated a systems biology approach to the identification of genetic drivers of fibrosis in the allograft and the potential application to native kidney. Through this mechanism they have identified several novel mediators of fibrosis which are being investigated further in humans and animal models. SHROOM3 is one such gene. An intronic SNP in SHROOM3 increases expression of SHROOM3 and drives fibrosis in human allograft recipients and murine models of CKD. Her research was published in The Journal of Clinical Investigation.

To read more about Dr. Murphy's research, please visit The Murphy Lab.

Genetic Variability and Outcomes in Transplantation

Organ transplantation results in increased life expectancy and lifestyle advantages as compared to all other modalities of kidney replacement therapy. Despite a marked improvement in rejection rates over the last decade, the improvement in long-term allograft survival remains modest. Recent advances from the Human Genome Project have identified numerous regions of genetic variability, both single-nucleotide polymorphisms (SNP's) and microsatellites regions, within genes relevant to transplantation. We have studied polymorphisms in chemokines and their receptor and costimulatory molecules and demonstrated three gene polymorphisms in CTLA-4 including one microsatellite dinucleotide repeat in the 3' untranslated region (3'-UTR) of the final exon (+642 (AT)n), and two SNP's located in the promoter (-318 C/T) and the first exon (+49 A/G) associated with functional effects and the incidence of autoimmune diseases. We have found an association with the (AT)92 and (AT)94 alleles of the +642 (AT)n microsatellite and acute rejection in both liver and kidney recipients. Analysis of CTLA-4 +49A/G demonstrated no association with acute rejection in either kidneys or livers. We have now extended this analysis to include the CTLA4 -318C/T and CD28 +17T/C SNP's for acute rejection and allograft survival. Homozygosity for the G allele of CTLA4 +49A/G significantly reduced 5 and 10-year graft survival, while the CTLA-4 +642(AT)n alleles associated with acute rejection (92, 94 and 100bp) were also associated with decreased graft survival and occurred more frequently in African American. Studies now focus on the relationship between haplotypes, graft survival and acute rejection. These studies form the basis for a larger prospective study in transplant recipients.

The Genomics of Chronic Allograft Rejection (GoCAR)

This study aims to investigate the mechanisms leading to the development of transplant glomerulopathy, chronic arteriopathy funded through the NIH/NIAID Genomics Consortium in Transplantation. The study examines the contribution of the direct and indirect pathways of allorecognition, and the development of de novo donor specific antibodies to this pathologic finding in a large prospective group of renal transplant recipients. The studies is examining the gene expression profile associated with the development of chronic rejection using microarray on protocol biopsies performed over two years following transplantation. In addition, a larger cohort of donor and recipient pairs are being enrolled to identify polymorphic variants of specific immunological genes which confer susceptibility to chronic rejection and the development of donor specific antibodies.

Patients have been enrolled in 5 clinical sites including Mount Sinai, Westmead Hospital Sydney, University Wisconsin – Madison Medical Center, University of Michigan Medical Center, Ann Arbor, and Northwestern Medical Center. The findings of this study will lead to important insights into the pathologic mechanisms mediating chronic allograft loss. Initial finding suggest that differential gene expression on normal 3 month protocol biopsies may be potentially used to immunologically stratify transplant recipients.

Risk factor for Renal Allograft Fibrosis

A systems biology approach to the identification of genetic drivers of fibrosis in the allograft and the potential application to native kidney. Through this mechanism we have identified several novel mediators of fibrosis which are being investigated further in humans and animal models. SHROOM3 is one such gene. An intronic SNP in SHROOM3 increases expression of SHROOM3 and drives fibrosis in human allograft recipients and murine models of CKD.

The purposes of this study are to determine the role of cell and antibody mediated responses in chronic rejection, to determine the gene expression profile associated with the development of chronic rejection, and to determine whether polymorphic variants of specific immunolog...

Schröppel B, Fischereder M, Ashkar R, Lin M, Krämer BK, Mardera B, Schiano T, Murphy B. The impact of polymorphisms in chemokine and chemokine receptors on outcomes in liver transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2002 Aug; 2(7).

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Below are financial relationships with industry reported by Dr. Murphy during 2016 and/or 2017.
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